Table 4.

Single variable and multivariable MR results of the genetic liability of alcohol, cannabis and lifetime smoking exposures on influenza, chronic lower respiratory diseases, and acute upper respiratory infections.

Outcome	Exposure	Single-variable MR					Multivariable MR
		N SNPs	OR	95% CI Lower	95% CI Upper	P-value	N SNPs	OR	95% CI Lower	95% CI Upper	P-value
Influenza
	Tobacco smoking	117	1.70	1.09	2.65	0.019	138	1.71	1.01	2.91	0.048
	Cannabis Use	36	1.01	0.91	1.13	0.836	142	1.17	0.97	1.41	0.093
	CUD	27	1.03	0.95	1.13	0.455	138	1.01	0.90	1.13	0.891
	Drinks Per Week	33	1.16	0.67	1.99	0.599	142	0.74	0.43	1.27	0.276
	AUD	11	1.08	0.95	1.24	0.240	138	1.00	0.91	1.10	0.955
Influenza and Pneumonia
	Tobacco smoking	116	1.53	1.25	1.87	4.13E−05	138	1.62	1.27	2.05	8.50E−05
	Cannabis Use	35	1.01	0.97	1.06	0.587	137	1.05	0.97	1.13	0.261
	CUD	27	1.05	1.01	1.09	0.013	138	0.99	0.94	1.04	0.662
	Drinks Per Week	33	0.97	0.75	1.25	0.812	137	0.97	0.77	1.22	0.780
	AUD	11	1.06	1.01	1.11	0.021	138	1.00	0.96	1.05	0.955
Chronic Lower Respiratory Diseases
	Tobacco smoking	113	2.23	1.73	2.87	5.69E−10	122	2.29	1.80	2.91	1.69E−11
	Cannabis Use	35	1.04	0.99	1.09	0.172	121	1.02	0.94	1.10	0.986
	CUD	27	1.05	1.01	1.10	0.015	122	1.02	0.97	1.07	0.533
	Drinks Per Week	31	0.91	0.69	1.20	0.492	121	0.89	0.68	1.15	0.020
	AUD	11	1.00	0.95	1.06	0.906	122	1.01	0.97	1.05	0.678
Acute Upper Respiratory Infections
	Tobacco smoking	116	1.32	1.09	1.61	0.004	130	1.47	1.19	1.82	3.52E−04
	Cannabis Use	34	1.02	0.97	1.06	0.484	135	1.06	0.99	1.14	0.115
	CUD	27	1.04	1.00	1.09	0.035	130	1.02	0.98	1.07	0.346
	Drinks Per Week	33	0.93	0.74	1.18	0.568	135	0.95	0.77	1.18	0.636
	AUD	11	0.99	0.95	1.04	0.699	130	0.98	0.95	1.02	0.355

Notes: Results from two sample SVMR inverse-variance weighted MR analysis; outliers identified by MR PRESSO global test and, for MVMR, MV MR Lasso penalization were removed; estimated associations reported as odds ratios with 95% confidence intervals. Boldface indicates statistical significance after correction for multiple comparisons (P < 0.000714). Genetic instruments selected from 5 GWASs, selection threshold P < 5 × 10⁻⁸ or P < 5 × 10⁻⁶ (CUD and AUD), clumped at linkage disequilibrium (LD) r² = .001 (10 000 kilobase pair window); N SNPs differs across outcomes depending on number of genetic instruments found in outcome GWASs. CUD cannabis use disorder, AUD alcohol use disorder, MR Mendelian randomization, GWAS genome wide association study, N SNPs number of single-nucleotide polymorphism (genetic instruments), OR odds ratio, CI confidence interval.